We propose to investigate antibodies to the phenylarsonate (Ar) and phenyltrimethylammonium (TMA) groups of defined cross-reactive idiotype (CRI) from inbred mice. The degree of homogeneity of their H and L chains will be investigated by isoelectric focusing and N-terminal amino acid sequence analysis. We have found that anti-Ar H chains of A/J mice, with or without CRI, are unblocked at the N-terminus and have a single or major residue at each position in the first framework region. We therefore plan to study sequences of H chains of anti-Ar antibodies of various strains to ascertain the rate of evolution (or conservation) of the germ line genes that appear to control framework regions. We will try to ascertain whether L chains of molecules with CRI, which exhibit some heterogeneity in the framework region, are identical or differ in the first hypervariable region. The chemical basis of the microheterogeneity of A/J anti-Ar antibodies with CRI will be explored. In a collaborative study an effort will be made to determine the complete sequence of the H chain. This is necessary for confirmation of the hypothesis that different L chains can combine with the same H chain to yield molecules with the same idiotype. The N-terminal sequences of L chains in C.AL-20mice, that possess the H chain allotype of the AL/N strain on a BALB/c background and produce CRI, will be investigated and compared with those of AL/N and A/J mice. Crossovers involving different V sub H genes or V sub H and C sub H genes will be sought; we have available 3 idiotypic markers to be used in these investigations. The frequency of lymphocyte precursors for cells producing anti-Ar antibodies with CRI in A/J mice will be determined and compared with the average concentration of circulating antibodies with CRI to determine whether a direct correlation exists. Methods will be explored to enhance the production of CRI. These may be of theoretical and practical interest. Idiotypes shared by mouse T cells reactive with histocompatibility antigens and alloantibodies will be investigated in an effort to define the numbers of idiotypes involved, and the degree of idiotypic cross-reactivity among individual animals.